From the Guidelines
Tissue transglutaminase (tTG) is a crucial enzyme in the diagnosis of celiac disease, and its role is well-established in the autoimmune response triggered by gluten consumption, as evident in a recent study published in 2024 1. The enzyme is the primary autoantigen targeted by antibodies in people with celiac disease when they consume gluten. When testing for celiac disease, doctors typically order a blood test that measures anti-tTG antibodies, which are present in about 98% of untreated celiac patients, as stated in a guideline published in 2024 1. The test is highly specific and sensitive, making it the preferred initial screening tool. For accurate results, patients should continue consuming gluten before testing, as following a gluten-free diet can lead to false negatives. Some key points to consider in the monitoring of celiac disease include:
- Type 2 transglutaminase antibody (TG2Ab) titres should be regularly monitored, as persistent elevation is suggestive of gluten exposure 1
- Nutritional testing in patients on a gluten-free diet (GFD) should be based on deficiencies observed at diagnosis, with special attention to iron, vitamin D and metabolic parameters 1
- Evaluation by a specialist dietician for the assessment of GFD adherence appears to perform better than adherence questionnaires 1 Beyond celiac disease, tTG has physiological functions including protein cross-linking, wound healing, and tissue repair, as noted in a study published in 2024 1. The enzyme is found in various body tissues and becomes externalized during inflammation or cellular damage, where it can modify gluten peptides in the intestine, creating complexes that trigger the autoimmune response characteristic of celiac disease. Understanding tTG's role helps explain why gluten triggers such specific immune reactions in susceptible individuals, and this knowledge is supported by guidelines from various scientific societies, including the American College of Gastroenterology (ACG) 1. In terms of diagnosis, all diagnostic serologic testing for celiac disease should be performed before a gluten-free diet is initiated, and Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody is the preferred test in persons older than two years, as recommended by the ACG 1. Overall, the diagnosis and management of celiac disease rely heavily on the understanding of tTG's role in the autoimmune response triggered by gluten consumption.
From the Research
t-Transglutaminase Overview
- t-Transglutaminase (tTG) is an enzyme that plays a crucial role in the pathogenesis of celiac disease (CD) 2, 3, 4.
- In CD, gluten induces the secretion of IgA-class autoantibodies that target tTG, which can be detected in the serum and small-intestinal mucosa 4.
- The presence of tTG autoantibodies is a hallmark of CD and is used as a diagnostic marker 2, 3, 5, 6.
Role of t-Transglutaminase in Celiac Disease
- tTG is involved in the immunopathology of CD, and autoantibodies against tTG can inhibit intestinal epithelial cell differentiation, induce intestinal epithelial cell proliferation, and increase epithelial permeability 4.
- The role of tTG autoantibodies in the disease pathogenesis is still a matter of debate, but they are thought to contribute to the development of the disease 4.
Diagnostic and Monitoring Applications
- tTG IgA antibodies are used as a diagnostic marker for CD, and their levels can be measured using various assays, including ELISA, FEIA, and CLIA 5, 6.
- The levels of tTG IgA antibodies can be used to monitor the response to a gluten-free diet (GFD) in CD patients, but the choice of assay can affect the results 6.
- Normalization of tTG IgA antibody levels can be delayed or incomplete in some patients on GFD, and the use of different assays can lead to discrepant results 6.
Clinical Implications
- The detection of tTG autoantibodies is essential for the diagnosis and monitoring of CD 2, 3, 5, 6.
- The choice of assay and interpretation of results should be considered when monitoring CD patients on GFD 6.
- Further research is needed to understand the role of tTG autoantibodies in CD and to develop more effective diagnostic and monitoring strategies 3, 6.